Indications of a common folding pattern for VDAC channels from all sources.

Previous research on the mitochondrial channel VDAC from the yeast S. cerevisiae had identified protein strands forming the wall of VDAC's aqueous pore. Here we report the results of analyzing the primary sequences of VDAC from various sources to see if the transmembrane folding pattern identified from this yeast is conserved for VDAC of different species. We analyzed the primary sequences of VDAC from higher plants, fungi, invertebrates, and vertebrates and found that all have a very similar "beta-pattern" profile with 12-15 peaks indicating potential sided beta strands that are candidates for protein strands forming the wall of the aqueous pore. All these VDAC sequences can be put into the 13 transmembrane strand folding pattern previously identified for yeast VDAC. These folding patterns agree with available experimental data: both electrophysiological and protease digestion data. Although the primary sequences of VDAC from very diverse organisms show low homology, sequence similarity in the proposed corresponding 13 transmembrane strands is substantial. Competing proposals utilizing 16 transmembrane beta strands are in conflict with electrophysiological experimental observations and violate the constraints on such strands, such as no charged amino acids facing the phospholipid membrane and sufficient number of residues to span the membrane.